Is neurotrophin-3 (NT-3): a potential therapeutic target for depression and anxiety?

ABSTRACT

Introduction: Neurotrophin-3 (NT-3) is thought to play a role in the neurobiological processes implicated in mood and anxiety disorders. NT-3 is a potential pharmacological target for mood disorders because of its effects on monoamine neurotransmitters, regulation of synaptic plasticity and neurogenesis, brain-derived neurotrophic factor (BDNF) signaling boosting, and modulation of the hypothalamic–pituitary–adrenal (HPA) axis. The mechanisms underlying NT-3 anxiolytic properties are less clear and require further exploration and definition.

Areas covered: The evidence that supports NT-3 as a pharmacological target for anxiety and mood disorders is presented and this is followed by a reflection on the quandaries, stumbling blocks, and future perspectives for this novel target.

Expert opinion: There is evidence for miRNAs being key post-transcriptional regulators of neurotrophin-3 receptor gene (NTRK3) in anxiety disorders; however, the anxiolytic properties of NT-3 need further examination and delineation. Moreover, NT-3 expression by non-neuronal cells and its role in brain circuits that participate in anxiety and mood disorders require further scrutiny. Further work is vital before progression into clinical trials can be realized.

KEYWORDS:

• Anxiety
• BDNF
• depression
• dopamine
• mood disorders
• neurotrophin-3
• NT-3
• neurotrophic factors
• noradrenaline
• Trk-C

Article Highlights

• NT-3 is thought to play a role in the neurobiological processes implicated in mood and anxiety disorders and is hence a potential pharmacological target

• NT-3 may exert antidepressant actions through its effects in monoamine neurotransmitters (serotonin and noradrenaline) and by regulating synaptic plasticity, neurogenesis, BDNF signaling, and the HPA axis.

• The mechanisms underlying NT-3 anxiolytic properties require further exploration and definition.

• More preclinical studies based on environmental and genetic models are necessary before progression to clinical studies

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors have received financial support from the Brazilian government funding agencies: FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Brazil), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior). The Neuropsychiatry Program is funded by the UTHealth Department of Psychiatry and Behavioral Sciences. A Teixeira is a CNPq fellowship recipient while AS Miranda is a 2019 ‘For Women in Science’ Grant Awardee from the L’Oreal Brazil-UNESCO- Brazilian Academy of Science (ABC).